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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Evaluation of cytotoxic, genotoxic and CYP450 enzymatic competition effects of Tanzanian plant extracts traditionally used for treatment of fungal infections
Basic and Clinical Pharmacology and Toxicology, Volume 102, No. 6, Year 2008
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Description
HIV-infected patients in sub-Saharan countries highly depend on traditional medicines for the treatment of opportunistic oral infections as candidiasis. Previous investigations on antifungal activity of medicinal plant extracts utilized by traditional healers in Tanzania have revealed 12 extracts with potent antifungal activity. Although the plants may be good candidates for new treatment opportunities, they can be toxic or genotoxic and could cause pharmacokinetic interactions when used concomitantly with antiretroviral agents. Therefore, we investigated the cytotoxicity, genotoxicity and cytochrome P450 interaction potential of these medicinal plants. Cytotoxicity was tested by Hoechst 33342, Alamar Blue, calcein-AM, glutathione depletion and O 2-consumption assays and genotoxicity by a Vitotox assay. Competition of the 12 extracts on substrate metabolism by CYP3A4, 2C9, 2C19 and 2D6 was tested with high-throughput CYP inhibition screening. Pregnane X receptor (PXR) activation was tested using Chinese hamster ovary cell lines expressing human PXR. Herbal extracts inducing high human PXR activation were tested for enhanced CYP3A4 mRNA levels with quantitative polymerase chain reaction. Genotoxicity was found for Jatropha multifida, Sterculia africana and Spirostachys africana. All plant extracts showed high cytotoxic effects in almost all tests. Potent competition with CYP3A4, 2D6, 2C9 and 2C19 was found for 75% of the herbal extracts. Spirostachys africana did not affect CYP2D6 and for S. africana and Turraea holstii no effect on CYP2D6 and CYP3A4 (DBF) was found. Nine plant extracts showed significant activation of human PXR, but only Agaura salicifolia, Turraea holstii and S. africana significantly induced CYP3A4 mRNA levels. These results indicate the possibility of potential medicinal plant-antiretroviral interactions. © 2008 The Authors.
Authors & Co-Authors
van den Bout-van den Beukel, Carolien J.P.
Netherlands, Nijmegen
Radboud University Medical Center
Hamza, Omar J.M.
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Moshi, Mainen Julius
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Matee, Mecky Isaac N.
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Mikx, F. H.M.
Netherlands, Nijmegen
Radboud University Medical Center
Burger, David M.
Netherlands, Nijmegen
Radboud University Medical Center
Koopmans, Peter P.
Netherlands, Nijmegen
Radboud University Medical Center
Verweij, Paul E.
Netherlands, Nijmegen
Radboud University Medical Center
Schoonen, Willem G.E.J.
Unknown Affiliation
van der Ven, André J.A.M.
Netherlands, Nijmegen
Radboud University Medical Center
Statistics
Citations: 37
Authors: 10
Affiliations: 2
Identifiers
Doi:
10.1111/j.1742-7843.2008.00225.x
ISSN:
17427835
e-ISSN:
17427843
Research Areas
Environmental
Health System And Policy
Infectious Diseases
Study Approach
Quantitative
Study Locations
Tanzania